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Open Access Research article

Soluble receptor activator of nuclear factor κB ligand/osteoprotegerin ratio is increased in systemic lupus erythematosus patients

Diana Carmona-Fernandes1, Maria José Santos12, Inês Pedro Perpétuo1, João Eurico Fonseca13 and Helena Canhão13*

Author Affiliations

1 Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Edifício Egas Moniz, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal

2 Rheumatology Department, Hospital Garcia de Orta, Av. Torrado da Silva, 2801-951 Almada, Portugal

3 Rheumatology and Bone Metabolic Diseases Department, Hospital de Santa Maria, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal

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Arthritis Research & Therapy 2011, 13:R175  doi:10.1186/ar3500

Published: 25 October 2011

Abstract

Introduction

Systemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG).

Our aim was to assess serum OPG and soluble RANKL (sRANKL) levels as well as sRANKL/OPG ratio in female SLE patients and compare it with female controls.

Methods

We have evaluated 103 SLE patients and 114 healthy controls, all Caucasian females. All participants underwent a clinical and laboratory evaluation. sRANKL and OPG were quantified in serum by ELISA based methods. sRANKL, OPG and sRANKL/OPG ratio levels were compared between SLE patients and age, sex and race matched healthy controls. For SLE patients, a multivariate analysis was performed, to find the possible predictors of the changes in sRANKL, OPG and sRANKL/OPG ratio levels.

Results

Although sRANKL levels did not differ between the two groups, serum OPG was lower in SLE patients (P < 0.001). This led to an increased sRANKL/OPG ratio (P = 0.010) in the patients' group.

The multivariate analysis was performed considering age and other clinical and laboratorial potential confounders for these variations in the SLE patients group. We have showed that age (P = 0.001) and levels of anti-Sm antibodies (P = 0.016) were independent predictors of sRANKL/OPG ratio variations in SLE patients. No relationship with therapy or disease activity measured by SLEDAI2K was found.

Conclusions

These results are suggestive of increased osteoclastic stimuli driven by the SLE disease mechanisms.

Keywords:
sRANKL; osteoprotegerin; systemic lupus erythematosus; osteoclastogenesis